4KQZ

structure of the receptor binding domain (RBD) of MERS-CoV spike

Summary for 4KQZ

• Entry DOI: 10.2210/pdb4kqz/pdb
• Related: 4KR0
• Descriptor: S protein, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: core subdomain, strand-dominated receptor binding motif, receptor binding, cd26, viral surface, viral protein
• Biological source: Human betacoronavirus 2c EMC/2012
• Total number of polymer chains: 2
• Total formula weight: 55640.32

Authors

Lu, G.,Hu, Y.,Wang, Q.,Qi, J.,Gao, F.,Li, Y.,Zhang, Y.,Zhang, W.,Yuan, Y.,Bao, J.,Zhang, B.,Shi, Y.,Yan, J.,Gao, G.F. (deposition date: 2013-05-15, release date: 2013-07-10, Last modification date: 2020-07-29)

Primary citation

Lu, G.,Hu, Y.,Wang, Q.,Qi, J.,Gao, F.,Li, Y.,Zhang, Y.,Zhang, W.,Yuan, Y.,Bao, J.,Zhang, B.,Shi, Y.,Yan, J.,Gao, G.F.
Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26.
Nature, 500:227-231, 2013

PubMed Abstract: The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 β-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein-protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition.

PubMed: 23831647
DOI: 10.1038/nature12328

Experimental method

X-RAY DIFFRACTION (2.514 Å)